Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of
green tea, can exert growth suppressive effect on human
pancreatic cancer cells by evoking apoptotic response. EGCG-induced apoptosis of
pancreatic cancer cells is accompanied by growth arrest at an earlier phase of cell cycle along with depolarization of mitochondrial membrane. In this report, using MIA PaCa-2 cells as in vitro model, we demonstrate EGCG-induced cell death involves activation of
caspase-8 and disappearance of intact 21 kDa
Bid protein. Furthermore, exogenous expression of dominant negative
caspase-8 or dominant negative FADD significantly abrogates apoptosis inducing ability of EGCG in MIA PaCa-2 cells.
RNase protection assay revealed upregulation of the members of
death receptor family, thus indicating the involvement of transmembrane extrinsic signaling in this
polyphenol triggered
pancreatic carcinoma cell death. Based on this, we examined the effect of EGCG and
tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) together on
pancreatic cancer cells. A synergistic increase in apoptosis and cleavage of
procaspase-3 was noted. Furthermore, clonogenic cell survival assay demonstrates the significant diminishment of MIA PaCa-2 cell proliferation in the presence of both EGCG and TRAIL. This combination treatment strategy has potential therapeutic advantage for
pancreatic carcinoma.